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Traumatic Brain Injury: What happens to the blood-brain barrier? Introduction Traumatic brain injury (TBI) is a major cause of death and disability worldwide for which there is no cure. Many patients who survive from TBI may experience permanent cognitive loss, behavioral issues, and emotional disturbances, which require daily medical or social attentions.[1, 2] It is believed that over 2% US population is experiencing TBI-associated disabilities which create an annual burden evaluated at $60 billion on direct (medical service) and indirect (loss of productivity) costs.[3, 4] Traumatic brain injury is complex which consists of a mechanical trauma (primary injury) and a resulting biochemical cascade (secondary injury), and lead to a wide diversity of symptoms.[5] The blood-brain barrier (BBB) is a highly specialized endothelial barrier which separates components of the circulating blood from neurons.[6] The BBB acts as the interface between the vascular system and the brain that restricts and regulates the exchange of substances.[7] The blood- brain barrier is responsible for the maintaining of homeostasis of the brain through regulating the chemical environment, the entry of xenobiotic and the immune cell transport.[8, 9] The concentration of water, ions, amino acids, hormones and neurotransmitters in the blood undergo fluctuations. If those fluctuations were allowed to occur in the brain it would lead to local disruption of signal propagation and uncontrolled neural activity.[8, 10] Interruption of cerebral blood flow would result in neuronal death.[11] The blood-brain barrier breakdown has often been documented in patients with TBI which may also be used as a biomarker in the clinic and drug trials.[12] The blood-brain barrier ... ...he activate local microglia.[63] Activated microglia can contribute to blood brain barrier opening.[64] Inflammation following blood brain barrier disruption after traumatic brain injury might be vital for the implementation of tissue repair and reorganization or even cell death.[65] Summary The pathological processes that develop following brain injury inevitably lead to neuronal death, which can be immediate or delayed. Blood brain barrier disruption, resulting in neuronal loss, might also influence the long-term traumatic brain injury complications which are characterized by neuronal death.[66, 67] Blood brain barrier breakdown is the central role of traumatic brain injury in the pathophysiology. Prevention of secondary damage following traumatic brain injury poses an important position in the treatment of traumatic brain injury or blood brain barrier breakdown.